Relapsed/Refractory AMLPhase 1/2CD33 CAR NKNCT07026942
Phase I/II Clinical Trial of Universal Donor CD33 CAR Natural Killer Cells for AML
A Phase 1/2 study testing Universal donor derived CD33 CAR-NK in people with Relapsed/Refractory AML, run by Nationwide Children's Hospital at 1 site in United States.
Trial summary
This phase 1/2 study is testing a new treatment for acute myeloid leukemia (AML) that has come back or has not responded to other treatments. The treatment uses specially modified immune cells (called CD33 CAR-NK cells) from a healthy, unrelated donor to attack the cancer. Read more about this study
- Who is it for?
- Ages 1 year to 39 years
- Conditions the study is for
- Relapsed/Refractory AML
- What is being tested?
- Universal donor derived CD33 CAR-NK
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2026to 1 Jul 2038
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 39 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with relapsed or primary refractory CD33+ AML, including:
- Patients with relapsed AML (patients in second or subsequent relapse, or any relapse after HSCT, are eligible).
- Refractory AML defined as failure to achieve a complete response after 2 cycles of induction or reinduction chemotherapy, including persistent MRD positivity.
- Patients with isolated CNS or extramedullary disease are eligible. Patients with CNS disease are excluded from the phase I dose escalation portion but are eligible for the phase II portion of the study.
- 1-39.99 years of age (note: the first three subjects treated AND the first subject on each dose level must be ≥ 16 years of age)
- Negative serum test to rule out pregnancy within 14 days prior to enrollment in females of childbearing potential
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- o Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator for 6 months after the last dose of chemotherapy and/or NK cell infusion
- Organ function requirements:
- Renal function: Creatinine ≤ 2 times the institutional upper limit of normal for age OR creatinine clearance > 60 ml/min/1.73m2 (measured by 24 hour- urine specimen or radioisotope GFR)
- Liver function: Total bilirubin ≤ 2 mg/dl (unless Gilbert's syndrome), AST and ALT ≤ 5 times the upper limit of normal (unless related to leukemic involvement). Upper limit of normal should be determined by the institutional defined normal laboratory range.
- Cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥20%. May be eligible after cardiology clearance if qualitatively normal function or repeat measures are normal.
- CNS: Patients with seizure disorder may be eligible if seizures are well controlled
- Pulmonary function: baseline oxygen saturation >92% on room air at rest
- Due to the risk of hematopoietic toxicity from CD33 targeting, enrolled subjects must have an allogeneic HCT donor identified and be eligible and willing to undergo a subsequent HSCT in the event of aplasia.
- All patients or their legal guardian must be able to understand and willing to sign a written informed consent document.
- All patients must consent to enroll in a separate long term follow up study for cell and gene therapy
Who cannot join
- Prior therapies:
- AML directed therapies in the 14 days prior to beginning treatment on this protocol (except for hydroxyurea) Note: There is no waiting period required for patients having received intrathecal cytarabine, methotrexate and/or hydrocortisone
- Gemtuzumab or other CD33-targeted antibody within 42 days of enrollment
- CNS radiation within 28 days of enrollment
- DLI or adoptive cell therapy within 30 days of enrollment
- Allogeneic SCT within 90 days of enrollment
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- Patients with CNS disease are excluded from the phase I portion of the study but are eligible for the phase II expansion phase.
- Patients on immunosuppressive therapy
- Patients must be off of systemic immunosuppressive therapy for at least 14 days prior to enrollment with no evidence of recurrent GVHD
- Patients on hydrocortisone for treatment of adrenal insufficiency are permitted on study
- Patients on corticosteroids ≤ 0.5mg/kg/day (prednisone equivalent) for any other indication are permitted on study
- Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements or in the opinion of the site PI would pose an unacceptable risk to the subject
- Patients who are breastfeeding
- Patients with prior solid organ transplantation
- Performance status: Karnofsky or Lansky Performance Scale (PS) < 50
- Uncontrolled infection, defined as an infection which has not resolved or does not show evidence of significant resolution after initiating appropriate therapy
- o Asymptomatic viremia such as CMV, HPV, BK virus, HCV, etc. is NOT considered as an exclusion criterion
- Uncontrolled arrhythmias or uncontrolled symptomatic cardiac disease
- Active acute or chronic GVHD of any grade at the time of enrollment. "Active GVHD" is defined as a patient who requires immunosuppressive therapy for control of their GVHD symptoms.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
Clelie Peck, 614-722-5634, Clelie.Peck@nationwidechildrens.org
About this study
Official title: A Phase I/II Clinical Trial Evaluating the Safety and Efficacy of Universal Donor CD33 CAR Natural Killer Cells for Treatment of Relapsed/Refractory Acute Myeloid Leukemia
This phase 1/2 study is testing a new treatment for acute myeloid leukemia (AML) that has come back or has not responded to other treatments. The treatment uses specially modified immune cells (called CD33 CAR-NK cells) from a healthy, unrelated donor to attack the cancer.
The first part of the study (Phase I) will focus on finding the safest and most effective dose. The second part (Phase II) will test how well the treatment works at that dose.
Read more
Patients will undergo screening, chemotherapy (Fludarabine and Cytarabine, in combination with Venetoclax) followed by the infusion of the CD33 CAR NK cells. Some patients may receive 2 doses of CD33 CAR NK cells infused 1 week apart. The investigator will let participants know if they will receive 1 or 2 doses. Patients will be hospitalized for the chemotherapy and CD33 CAR NK cell infusion for close monitoring and will remain in the hospital until blood counts recover. If patients are discharged from the hospital before day 35, they will be followed in clinic weekly for blood work and a physical exam.
A bone marrow biopsy will be performed around day 28-35 to see if the patient's leukemia is in remission. Lumbar puncture or imaging may also be done if the study doctor thinks it is necessary.
Patients will continue to be followed for research studies and clinical outcomes (leukemia relapse, survival) for 1 year. After 1 year, patients will have completed their study participation, but can be monitored for up to 15 years for potential long term side effects of the cell therapy. Some patients may undergo a bone marrow transplant after the study treatment. Patients who proceed to bone marrow transplant will have one blood sample drawn about a month after the transplant and then will have completed study participation.
Read the detailed description
This is a phase I/II study designed to determine the safety and estimate the efficacy of CD33 CAR-NK cells combined with FLA-VEN chemotherapy in patients age 1-39.99 with relapsed or refractory acute myeloid leukemia. This study will be performed in two phases: a dose-finding phase and a phase II expansion phase to further study safety and estimate efficacy. To determine the recommended phase II dose investigators will utilize a Bayesian optimal interval (BOIN) dose escalation design. Once a RP2D is established, a phase II expansion cohort of 24 total patients will be enrolled to evaluate efficacy and correlative data while also continually gathering data on safety and toxicity.
Manufacturing of the CD33 CAR NK Cells:
NK cells are derived from the peripheral blood of universal donors with desirable HLA/KIR types and CMV status, modified by CRISPR/Cas9 targeting the CD38 locus, using AAV6 vector to insert a CD33-targeted CAR gene into the CD38 locus, and expanded in number.
Dose Levels
- Dose level 1: 1 x 10^7 CD33 CAR-NK cells/kg
- Dose level 2: 3 x 10^7 CD33 CAR-NK cells/kg
- Dose level 3: 1 x 10^8 CD33 CAR-NK cells/kg
- Dose level 4: 2 doses of 1 x 10^8 CD33 CAR-NK cells/kg
Chemotherapy:
Days 1-5: Fludarabine 30 mg/m2/d, cytarabine 2g/m2/d Days 1-21: Venetoclax Day 7: CD33 CAR NK infusion Day 14; CD33 CAR NK infusion (for patients on DL4)
Patients will be admitted to the hospital for 4-5 weeks during each cycle of treatment for count nadir and recovery.
- Conditions
- Relapsed/Refractory AML
- Being tested
- Universal donor derived CD33 CAR-NK
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Universal donor derived CD33 CAR-NKBiological
Universal donor derived CD38KO CD33 CAR-NK manuctured on-site. The NK cells are derived from the peripheral blood of universal donors with desirable HLA/KIR types and CMV status, modified by CRISPR/Cas9 targeting the CD38 locus, using AAV6 vector to insert a CD33-targeted CAR gene into the CD38 locus, and expanded in number.
| Study group | Role | What they receive |
|---|---|---|
| CD33 CAR NK Cells | Experimental | Patients will undergo 5 days of lymphodepleting chemotherapy (Fludarabine and Cytarabine) along with oral Venetoclax given from days 1-21 of the cycle.
CD33 CAR NK cells will be infused on day 7 (and day 14 for dose level 4).
Dose Levels
* Dose level 1: 1 x 10^7 CD33 CAR-NK cells/kg
* Dose level 2: 3 x 10^7 CD33 CAR-NK cells/kg
* Dose level 3: 1 x 10^8 CD33 CAR-NK cells/kg
* Dose level 4: 2 doses of 1 x 10^8 CD33 CAR-NK cells/kg Receives: Biological: Universal donor derived CD33 CAR-NK |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I : Safety and recommended phase 2 dose
To determine the safety and recommended phase 2 dose of CD33 CAR-NK cells in patients with relapsed/refractory AML investigators will monitor the incidence and severity of adverse events and the rate of dose limiting toxicities.
Measured: From the first CD33 CAR NK cell infusion until 28 days after the last CAR NK cell dose.
Phase II: Efficacy of CD33 CAR NK cells
To estimate the efficacy of CD33 CAR-NK cells delivered at the RP2D with FLA-VEN chemotherapy, the investigators will determine the complete response rate.
Measured: Day 35
Secondary outcomes (4)
Overall survival, event free survival and duration of remission
To estimate the overall survival, event free survival, and duration of remission in patients who do not proceed to HSCT.
Measured: 1 year
Depth of remission
To determine the percentage of patients who achieve molecular remission and/or MRD negative remission by flow cytometry.
Measured: Day 35
Events of special interest
To determine the rate of events of special interest including: Cytokine Release Syndrome, Immune Effector Cell Neurotoxicity Syndrome, Immune Effector Cell-Associated Hemophagocytic Lymphohistiocytosis-Like Syndrome, hepatic VOD, primary graft failure (in patients who undergo HSCT)
Measured: 8 weeks post CAR NK, day +30 post HSCT
Neutrophil recovery
To evaluate the median time to neutrophil and platelet recovery
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2025
- Study start1 Apr 2026 (estimated)
- Primary completion1 Jul 2032 (estimated)
- Study completion1 Jul 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsed/Refractory AMLStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A single-arm, unblinded, dose escalation study
- Masking
- None (open label)
- Enrolment
- 42 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Margaret Lamb, Nationwide Children's Hospital
- Investigators
- Margaret Lamb, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07026942
- Sponsor's protocol ID
- CD33 CAR NK
- Acronym
- CD33 CAR NK
- Status last verified
- Nov 2025
- First submitted
- 10 Jun 2025
- Last updated
- 12 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 12 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Clinical Trial Evaluating the Safety and Efficacy of Universal Donor CD33 CAR Natural Killer Cells for Treatment of Relapsed/Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT07026942
- Acronym / sponsor ID
- CD33 CAR NK / CD33 CAR NK
- Conditions
- Relapsed/Refractory AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 42 participants (estimated)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- 1 Apr 2026 (estimated)
- Primary completion
- 1 Jul 2032 (estimated)
- Study completion
- 1 Jul 2038 (estimated)
- First posted
- 18 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 1/2 study is testing a new treatment for acute myeloid leukemia (AML) that has come back or has not responded to other treatments. The treatment uses specially modified immune cells (called CD33 CAR-NK cells) from a healthy, unrelated donor to attack the cancer.
The first part of the study (Phase I) will focus on finding the safest and most effective dose. The second part (Phase II) will test how well the treatment works at that dose.
Patients will undergo screening, chemotherapy (Fludarabine and Cytarabine, in combination with Venetoclax) followed by the infusion of the CD33 CAR NK cells. Some patients may receive 2 doses of CD33 CAR NK cells infused 1 week apart. The investigator will let participants know if they will receive 1 or 2 doses. Patients will be hospitalized for the chemotherapy and CD33 CAR NK cell infusion for close monitoring and will remain in the hospital until blood counts recover. If patients are discharged from the hospital before day 35, they will be followed in clinic weekly for blood work and a physical exam.
A bone marrow biopsy will be performed around day 28-35 to see if the patient's leukemia is in remission. Lumbar puncture or imaging may also be done if the study doctor thinks it is necessary.
Patients will continue to be followed for research studies and clinical outcomes (leukemia relapse, survival) for 1 year. After 1 year, patients will have completed their study participation, but can be monitored for up to 15 years for potential long term side effects of the cell therapy. Some patients may undergo a bone marrow transplant after the study treatment. Patients who proceed to bone marrow transplant will have one blood sample drawn about a month after the transplant and then will have completed study participation.
Detailed description
This is a phase I/II study designed to determine the safety and estimate the efficacy of CD33 CAR-NK cells combined with FLA-VEN chemotherapy in patients age 1-39.99 with relapsed or refractory acute myeloid leukemia. This study will be performed in two phases: a dose-finding phase and a phase II expansion phase to further study safety and estimate efficacy. To determine the recommended phase II dose investigators will utilize a Bayesian optimal interval (BOIN) dose escalation design. Once a RP2D is established, a phase II expansion cohort of 24 total patients will be enrolled to evaluate efficacy and correlative data while also continually gathering data on safety and toxicity.
Manufacturing of the CD33 CAR NK Cells:
NK cells are derived from the peripheral blood of universal donors with desirable HLA/KIR types and CMV status, modified by CRISPR/Cas9 targeting the CD38 locus, using AAV6 vector to insert a CD33-targeted CAR gene into the CD38 locus, and expanded in number.
Dose Levels
- Dose level 1: 1 x 10^7 CD33 CAR-NK cells/kg
- Dose level 2: 3 x 10^7 CD33 CAR-NK cells/kg
- Dose level 3: 1 x 10^8 CD33 CAR-NK cells/kg
- Dose level 4: 2 doses of 1 x 10^8 CD33 CAR-NK cells/kg
Chemotherapy:
Days 1-5: Fludarabine 30 mg/m2/d, cytarabine 2g/m2/d Days 1-21: Venetoclax Day 7: CD33 CAR NK infusion Day 14; CD33 CAR NK infusion (for patients on DL4)
Patients will be admitted to the hospital for 4-5 weeks during each cycle of treatment for count nadir and recovery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A single-arm, unblinded, dose escalation study
| Arm | Type | Receives |
|---|---|---|
| CD33 CAR NK Cells | Experimental | Biological: Universal donor derived CD33 CAR-NKPatients will undergo 5 days of lymphodepleting chemotherapy (Fludarabine and Cytarabine) along with oral Venetoclax given from days 1-21 of the cycle. CD33 CAR NK cells will be infused on day 7 (and day 14 for dose level 4). Dose Levels * Dose level 1: 1 x 10^7 CD33 CAR-NK cells/kg * Dose level 2: 3 x 10^7 CD33 CAR-NK cells/kg * Dose level 3: 1 x 10^8 CD33 CAR-NK cells/kg * Dose level 4: 2 doses of 1 x 10^8 CD33 CAR-NK cells/kg |
Who may qualify
- Ages
- 1 year to 39 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (16 listed)
- Patients with relapsed or primary refractory CD33+ AML, including:
- 1-39.99 years of age (note: the first three subjects treated AND the first subject on each dose level must be ≥ 16 years of age)
- Negative serum test to rule out pregnancy within 14 days prior to enrollment in females of childbearing potential
- o Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator for 6 months after the last dose of chemotherapy and/or NK cell infusion
- Organ function requirements:
Key exclusion criteria (19 listed)
- Prior therapies:
- Uncontrolled, symptomatic, intercurrent illness or social situations that would limit compliance with study requirements or in the opinion of the site PI would pose an unacceptable risk to the subject
- Patients who are breastfeeding
- Patients with prior solid organ transplantation
- Performance status: Karnofsky or Lansky Performance Scale (PS) < 50
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Universal donor derived CD33 CAR-NKUniversal donor derived CD38KO CD33 CAR-NK manuctured on-site. The NK cells are derived from the peripheral blood of universal donors with desirable HLA/KIR types and CMV status, modified by CRISPR/Cas9 targeting the CD38 locus, using AAV6 vector to insert a CD33-targeted CAR gene into the CD38 locus, and expanded in number. | Biological | CD33 CAR NK Cells |
Primary outcome
Phase I : Safety and recommended phase 2 dose
Time frame: From the first CD33 CAR NK cell infusion until 28 days after the last CAR NK cell dose.
To determine the safety and recommended phase 2 dose of CD33 CAR-NK cells in patients with relapsed/refractory AML investigators will monitor the incidence and severity of adverse events and the rate of dose limiting toxicities.
Phase II: Efficacy of CD33 CAR NK cells
Time frame: Day 35
To estimate the efficacy of CD33 CAR-NK cells delivered at the RP2D with FLA-VEN chemotherapy, the investigators will determine the complete response rate.
4 secondary outcomes
Overall survival, event free survival and duration of remission
Time frame: 1 year
Depth of remission
Time frame: Day 35
Events of special interest
Time frame: 8 weeks post CAR NK, day +30 post HSCT
Neutrophil recovery
Time frame: 1 year
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Nov 2025.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Margaret Lamb, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Universal donor derived CD33 CAR-NK in people with Relapsed/Refractory AML, run by Nationwide Children's Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 12 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clelie Peck (614-722-5634, Clelie.Peck@nationwidechildrens.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I : Safety and recommended phase 2 dose (time frame: From the first CD33 CAR NK cell infusion until 28 days after the last CAR NK cell dose.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Nov 2025.